1. Field Of The Invention
This invention relates to a process for manufacturing d,l-.beta.-benzoylamino-isobutyric acid.
As known, d,l-.beta.-benzoylamino-isobutyric acid is a valuable intermediate in the preparation of pharmaceuticals, e.g. triamcinolone acetonide esters which exhibit in topical use an effective antiphlogistic action. More particularly, this invention relates to a process for manufacturing d,l-.beta.-benzoylamino-isobutyric acid whereby industrial application is facilitated since the starting materials employed during synthesis are widely used, readily available and quite inexpensive materials, and the reaction is carried out completely at atmospheric pressure. Moreover, by applying the process of this invention, a high purity product at a low cost with excellent yields is obtained.
2. Description Of The Prior Art
As disclosed in the prior art, the preparation of d,l-.beta.-benzoylamino-isobutyric acid entails a cumbersome, multistep, low-yield process resulting in an expensive product which still requires complex purification procedures before being suitable for industrial application or further processing.
Floyd P. Kupiecki and Minor J. Coon in Biochemical Preparations, 1, 20 (1969) disclose the synthesis of .beta.-aminoisobutyric acid, an indispensable intermediate in the prior art preparation of d,l-.beta.-benzoylamino-isobutyric acid. In accordance with this disclosure, .alpha.-bromopropionic acid is reacted at 45.degree.-50.degree. C. with potassium cyanide to obtain .alpha.-cyanopropionic acid in a yield of only 52% based on .alpha.-bromopropionic acid which, before being subjected to further processing, has to be carefully separated from the unreacted bromo-acid by distillation under reduced pressure. The .alpha.-cyanopropionic acid is then hydrogenated under pressure in the presence of platinum oxide; the hydrogenation requires about 6 hours. After removal of the spent catalyst by filtration and several subsequent steps of concentration, neutralization and filtration, a pasty residue is obtained which by a first crystallization and recrystallization from ethanol gives .beta.-aminoisobutyric acid, in a yield of only 58%, based on .alpha.-cyanopropionic acid.
To obtain d,l-.beta.-benzoylamino-isobutyric acid, the .beta.-aminoisobutyric acid has finally to be reacted with a benzoyl halide, usually benzoyl chloride, under conventional reaction conditions.